Our previous research on the interaction of chemical carcinogens with transforming DNA has demonstrated conclusively that ultimate carcinogens are mutagenic. With this system and the naturally-synchronous plasmodium, Physarum polycephalum, we have obtained clear physicochemical and genetic evidence of repair of lesions induced in DNA by such carcinogens. Since chemical carcinogens are strongly implicated causally in human cancer, we have extended these investigations by developing a system for quantitating the cytotoxic and mutagenic effects of carcinogens in normal diploid human cells in culture and in cells which are defective in DNA repair capabilities (xeroderma pigmentosum) and for determining the role of DNA repair on such interaction. With this system, as an assay, we will investigate several well-characterized actions of carcinogens, viz: (1) the effect of carcinogen treatment of normally-repairing diploid human cells or repair-deficient human cells on the expression of viral specific information and/or the ability to be transformed by exposure to DNA tumor viruses, DNA of such viruses, or exogenous DNA containing viral sequences of RNA tumor viruses. (2) The relationship between carcinogens and co-carcinogens in interacting with human cells to cause cytotoxic and mutagenic effects and induce DNA repair. (3) The role of cell cycle phase on the interaction of carcinogens with synchronized populations of diploid human cells. (4) The ability of agents which induce activating enzymes to increase the extent of cytotoxic and mutagenic interaction of carcinogens with these cells. Such studies will give information on the fundamental interaction of carcinogens with human cells and may provide insight as to why such cells are refractory to chemical transformation in vitro, but susceptible to transformation by DNA tumor viruses. BIBLIOGRAPHIC REFERENCE: Maher, V.M., McCormick, J.J., Grover, P.L. and Sims, P. Effect of DNA Repair on the Cytotoxicity and Mutagenicity of Polycyclic Hydrocarbon Derivatives in Normal and Xeroderma Pigmentosum Human Fibroblasts. Mutation Res. 43; 117-138 (1977).